Recently, we have demonstrated that T helper cell differentiation is regulated by beta-catenin and TCF1. We show that TCF1 negatively regulates IFN-gamma expression and promotes skewing toward Th1 lineage, while beta-catenin and TCF1 together work to induce IL-4 production thereby promoting Th2 fate. In the future, we will determine if this pathway impacts development of Th17 cells. In addition, we will use well-established mouse models to evaluate the effect of manipulating the beta-catenin-TCF signaling pathway in pathogenesis of asthma and infections such as T. muris or Leishmania. We will also evaluate the effect of these mutants in a multiple sclerosis mouse model (EAE). Together, these studies may provide insight in the development of bio-medical tools to combat T-helper cell-dependent diseases in humans.